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G-CSF exerts dual effects on endothelial cells--opposing actions of direct eNOS induction versus indirect CRP elevation

Cited 26 time in Web of Science Cited 27 time in Scopus
Authors
Park, Kyung-Woo; Kwon, Yoo-Wook; Cho, Hyun-Jai; Shin, Jung-Im; Kim, Yong-Jin; Lee, Sang Eun; Youn, Seock-Won; Lee, Hyun-Chae; Kang, Hyun-Jae; Shaul, Philip W; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo
Issue Date
2008-08-05
Publisher
Elsevier
Citation
J Mol Cell Cardiol. 2008; 45(5) :670-8.
Keywords
1-Phosphatidylinositol 3-Kinase/metabolismC-Reactive Protein/*metabolismCell LineCell MovementEndothelial Cells/*metabolismGranulocyte Colony-Stimulating Factor/*metabolismHepatocytes/metabolismHumansInterleukin-6/metabolismModels, BiologicalMonocytes/metabolismNitric Oxide/metabolismNitric Oxide Synthase Type III/*metabolismTranscription, GeneticWound Healing
Abstract
Granulocyte-colony stimulating factor (G-CSF) has been shown to have protective effects in the heart and brain. However, it may also be involved in the acute inflammatory response which may be harmful. The effects of G-CSF on endothelial cells (ECs) and the vasculature are mostly unknown. To study the possible dual effects of G-CSF on ECs, we investigated whether G-CSF induces release of C-reactive protein (CRP) by hepatocytes and whether the direct beneficial effects of G-CSF could protect ECs from the detrimental effects of CRP. G-CSF treatment significantly induced monocytes to produce IL-6, and culture supernatants of G-CSF-stimulated monocytes induced CRP production in hepatocytes. On the other hand, G-CSF directly promoted EC proliferation and migration and reversed the deleterious effects of CRP. In mechanistic analyses, G-CSF increased not only the protein expression of endothelial nitric oxide synthase (eNOS), but also its transcription. Furthermore, it enhanced eNOS phosphorylation and activation, leading to increased production of NO. Thus, G-CSF reversed the attenuated production of NO by CRP. These effects of G-CSF on eNOS transcription, translation, and activation were blunted by the PI3K inhibitor, suggesting that EC protective effects of G-CSF were associated with the activation of the Akt/eNOS pathway. In conclusion, although G-CSF induces an inflammatory reaction leading to CRP production, it has direct beneficial effects protecting ECs from the deleterious effects of CRP through activation of Akt/eNOS pathway, leading to an increase in NO production. Our data suggests that G-CSF may exert dual opposing effects on endothelial cells.
ISSN
1095-8584 (Electronic)
Language
English
URI
http://hdl.handle.net/10371/62198
DOI
https://doi.org/10.1016/j.yjmcc.2008.07.002
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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